The extracellular levels of lysosomal enzymes have been implicated in the development of uncontrolled cellular growth, tumor invasiveness and the inflammatory response. Previous work from our laboratory has uncovered a mannosyl/glucosyl specific receptor system associated with macrophage plasma membranes which mediates adsorptive pinocytosis (uptake) of lysosomal glycosidases and glycoproteins having mannose in the terminal position. The receptor also recognizes glucose and N-acetylglucosamine but not galactose. We propose to study the mode and mechanism of uptake of lysosomal enzymes by macrophages. The regulation of the receptor will be studied by following ligand binding and by preparing receptor-specific antibody. The interrelationships between ligand and internalization and lysosomal enzyme biosynthesis and turnover will be investigated.